White matter hyperintensity presence, quantity, and location exhibits no association with motor and non-motor manifestations of PD.

INTRODUCTION: Nonspecific areas of brain white matter hyperintensity (WMH) are commonly found in the elderly. Some studies have shown that the presence, quantity, and location of WMHs may be associated with the development of cognitive and motor decline in patients with Parkinson's disease (PD), but the results remain controversial. This study aimed to evaluate the relationship of WMH to motor and non-motor symptoms, including dysautonomia and rapid eye movement sleep behavior disorder (RBD), in patients with PD. METHODS: Brain magnetic resonance images were acquired from 120 patients diagnosed with PD and analyzed for WMH classification and quantification. Motor symptoms were quantified using sub-scores of the Movement Disorder Society-Unified Parkinson Disease Rating Scale (MDS-UPDRS)-III. Dysautonomia was evaluated by autonomic reactivity tests, and polysomnography was used for the diagnosis of RBD. RESULTS: Age, total value of the MDS-UPDRS-III tremor sub-score, and the presence of dysautonomia were found to be linearly positively associated. Specifically, the duration of PD was positively associated with rigidity, bradykinesia, axial symptoms, prevalence of dysautonomia, and RBD sub-scores. However, in the multivariate analysis adjusted for variables of interest, no statistical significance was found for any of the models. CONCLUSION: The presence, quantity, and location of WMH were not associated with the analyzed motor and non-motor manifestations of PD.

The Effect of Cannabidiol for Restless Legs Syndrome/Willis-Ekbom Disease in Parkinson's Disease Patients with REM Sleep Behavior Disorder: A Post Hoc Exploratory Analysis of Phase 2/3 Clinical Trial.

Background: Cannabidiol (CBD) is one of the main nonpsychoactive components of Cannabis sativa and may represent an alternative treatment for Restless Legs Syndrome/Willis-Ekbom Disease (RLS/WED) in patients with Parkinson's disease (PD) and REM (Rapid Eye Movement) sleep behavior disorder (RBD). Objective: Our purpose was a post hoc exploratory analysis to evaluate the CBD's efficacy to improve the severity of RLS/WED symptoms in patients with PD and RBD. Methods: A post hoc exploratory analysis of a phase II/III, a parallel, double-blind, placebo-controlled clinical trial was conducted in 18 patients with RLS/WED and PD plus RBD associated. Six patients were randomized to the CBD group in doses of 75-300 mg, and twelve received placebo capsules. They were followed up for 14 weeks. The primary outcome was the severity of RLS/WED by Restless Legs Syndrome Rating Scale of the International Restless Legs Syndrome Study Group (IRLSSG). Results: CBD showed no difference in relationship to placebo for primary and secondary outcomes. Conclusion: CBD showed no reduction in the severity of RLS/WED manifestation in patients with PD and RBD.

Inflammatory markers and depression in Parkinson's disease: a systematic review.

BACKGROUND: Parkinson's disease (PD) patients experience non-motor symptoms (NMS), which may appear before motor manifestations. The most common NMS is depression, affecting about 30-40% of PD patients. Both PD and depression are associated with an increased inflammatory burden, with studies showing elevation of diverse inflammatory markers in patients with both conditions. METHODS: A systematic review was conducted in PubMed and PsycINFO databases to investigate what inflammatory markers are associated with PD depression (PDD). Only studies in English that measured inflammatory markers and analyzed against depression scores in PD patients were included. RESULTS: A total of 1132 articles were retrieved, and 14 entries were found to be eligible. Twelve were cross-sectional studies, one was a cohort, and one was a non-randomized controlled trial. IL-17A was the only marker strongly associated with PDD, while studies assessing sIL-2R and serum amyloid A found a moderate correlation. C-reactive protein, IL-10, tumor necrosis factor-α, monocyte chemoattractant protein-1, and IL-6 yielded conflicting results. Their possible roles in PDD are discussed. PDD was also related to longer disease duration and other NMS, such as anxiety, fatigue, dementia, REM sleep behavior disorder, and autonomic dysfunction. CONCLUSION: We suggest that these markers may be used for distinguishing isolated depression from that related to neurodegeneration, especially in individuals that concurrently present with other known prodromal symptoms of PD and other α-synucleinopathies. However, future prospective studies are warranted to confirm this hypothesis.

Actualización en enfermedad con cuerpos de Lewy / Update in Lewy body disease

La enfermedad con cuerpos de Lewy incluye 2 entidades que podrían ser consideradas variantes clínicas de una misma patología: la demencia con cuerpos de Lewy y la demencia en enfermedad de Parkinson. Con la finalidad de describir correctamente lo que sucede en la evolución de la enfermedad se divide el cuadro en etapa prodrómica y de demencia propiamente dicha. La primera está clínicamente representada por aquel período en el cual, si bien el paciente exhibe algunos signos y síntomas propios de la enfermedad, no reúne criterios de demencia. A pesar de ser difícil de definir y por carecerse todavía de contundentes datos clínicos y biomarcadores, se caracteriza principalmente por deterioro leve selectivo en función atencional ­ visuoespacial, trastorno del sueño REM y disautonomía‒. La segunda etapa está claramente caracterizada en los criterios de consenso del año 2005. Recientemente hemos publicado la validación de un instrumento llamado ALBA Screening Instrument, que permite diagnosticar con alta sensibilidad y especificidad la enfermedad aun en etapas tempranas y diferenciarla de otras patologías semejantes. La tomografía por emisión de positrones (PET) para transportador de dopamina es el procedimiento de referencia (gold standard) del diagnóstico. El tratamiento sintomático con anticolinesterásicos y neurolépticos atípicos favorece una buena evolución de la enfermedad y es fundamental tener en cuenta evitar medicamentos que pueden dañar gravemente a los pacientes como los anticolinérgicos y antipsicóticos típicos. Los avances en el diagnóstico y la difusión del impacto de esta enfermedad en la población contribuirán a generar mayores esfuerzos de investigación para hallar un tratamiento eficaz, preventivo o curativo o de ambas características. (AU)

Lewy body disease includes 2 entities that could be considered clinical variants of the same pathology: Dementia with Lewy bodies and Parkinson's disease Dementia. Two stages of the disease are described in this review, a prodromal stage and one of explicit dementia. The first one is clinically represented by that period in which, the patient exhibits some typical features of the disease, but not dementia criteria. Despite being difficult to define the prodromal stage and that strong clinical data and biomarkers are still lacking, there is evidence to characterize it mainly by mild selective impairment in attention and visuo-spatial function, REM sleep disorder and dysautonomia. The second stage is clearly characterized in the known consensus criteria of 2005. We have recently published the validation of an instrument called ALBA Screening Instrument which showed a high sensitivity and specificity for diagnosis of the disease even in the early stages. It´s useful to differentiate the disease from other similar pathologies. Positron Emission Tomography for dopamine transporter is the gold standard of diagnosis in life. Symptomatic treatment with anticholinesterases and atypical neuroleptics help patients in their evolution of the disease. Anticholinergics and typical antipsychotics are agents to avoid in the treatmen of the disease because can severely damage patients. Future advances in the diagnosis and dissemination of the knowledge of the disease will contribute to generate greater research efforts to find an effective preventive and / or curative treatment. (AU)

Expression of prion protein in the cerebrospinal fluid of patients with Parkinson's disease complicated with rapid eye movement sleep behavior disorder.

Parkinson's disease (PD) is one of the most common neurodegenerative diseases and mainly manifests with decreasing numbers of dopaminergic neurons. Rapid eye movement (REM) sleep behavior disorder (RBD) has an incidence of 15-47% in all PD patients. Prion proteins (PrPs), which are expressed in both neurons and glial cells of the brain, are believed to be correlated with abnormal neurological functions, although their role in PD-related sleeping disorders remains unclear. We therefore investigated the expressional profiles of PrP in PD patients with RBD. Quantitative real-time polymerase chain reaction and western blotting were used to detect the mRNA and protein levels of PrP, respectively, in the cerebrospinal fluid (CSF) of PD patients with RBD, PD patients without sleeping disorder, and healthy people (N = 23 each). We investigated the correlation between the CSF PrP level and sleeping behavior in PD patients. Patients with PD complicated with RBD had significantly elevated CSF PrP expression levels (both mRNA and protein) compared with either PD patients without sleeping disorder or healthy individuals (P < 0.05 in both cases). There is elevated expression of PrP in the CSF of PD patients with RBD. This may benefit the diagnosis of PD-related RBD.

Rapid Eye Movement Sleep Behavior Disorder in Paraneoplastic Cerebellar Degeneration: Improvement with Immunotherapy.

STUDY OBJECTIVES: To report two female patients with paraneoplastic cerebellar degeneration (PCD) related to breast cancer that presented with rapid eye movement-sleep behavior disorder (RBD) and improved sleep symptoms with immunotherapy. METHODS: The two patients were evaluated through clinical scale and polysomnography before and after therapy with intravenous immunoglobulin. RESULTS: RBD was successfully treated with immunotherapy in both patients. Score on the RBD screening questionnaire dropped from 10 to 1 or 0, allied with the normalization of polysomnographic findings. CONCLUSIONS: A marked improvement in RBD after immunotherapy in PCD raises the hypothesis that secondary RBD may be an immune-mediated sleep disorder.

Plasma urate in REM sleep behavior disorder.

BACKGROUND: Rapid eye movement (REM) sleep behavior disorder (RBD) is associated with a high risk of developing Parkinson's disease (PD). Higher urate levels are associated with a lower risk of PD. We conducted a study to evaluate plasma urate levels in patients with RBD and their role in the development of PD. METHODS: We evaluated plasma urate levels in a cohort of 24 patients with idiopathic RBD. Patients were divided into 2 groups according to the presence or absence of PD. Other known markers of the risk of developing PD, such as olfaction testing, and substantia nigra (SN) hyperechogenicity, were evaluated in the 2 groups. RESULTS: No differences were observed regarding age, years of evolution of the RBD, SN hyperechogenicity, or plasma urate levels between the 2 groups. In patients without PD, there was a positive correlation between years of evolution of RBD and the levels of uric acid (R(2) =0.88). Patients without PD and those who had more than 5 years of RBD exhibited higher levels of uric acid than patients with PD (P=0.02). CONCLUSIONS: Higher levels of plasma urate were associated with a longer duration of RBD without converting to PD. Future prospective studies would be needed to confirm this finding. Disorder Society

Long-duration Parkinson's disease: role of lateralization of motor features.

BACKGROUND: A mean of 10 years elapse before patients with Parkinson's disease (PD) reach Hoehn & Yahr (H&Y) stage 4, and 14 years for stage 5. A small proportion of PD patients survive and are ambulatory for ≥ 20 years. We sought to identify features associated with long-duration PD (dPD). METHODS: This five-center, case-control study compared 136 PD patients with ≥ 20 years of duration and H&Y stage ≤ 4 (dPD) to 134 H&Y-, age- and gender-matched PD patients between 10 and 15 years of disease (cPD). RESULTS: By study design, there were no between-group differences in age, gender and H&Y. dPD subjects were younger at onset (p < 0.0001), had more psychosis (p: 0.038), were receiving higher levodopa equivalent daily doses (p: 0.02), were predominantly left-handed (p: 0.048), and had greater frequency of left-sided onset (p: 0.015) compared to cPD subjects. Both groups had similar rates of resting tremor, dementia and REM sleep behavior disorder. CONCLUSIONS: Early disease onset, left-handedness and left-sided onset are associated with long disease and ambulatory PD survival. The neurobiological basis of the prognostic value of lateralization deserves further investigation.

Sleep disorder: a possible cause of attention deficit in children and adolescents with Chiari malformation type II.

BACKGROUND: Attention deficit may be related to sleep disorders in Chiari malformation type II (CMII). Our aim is identify sleep disorders and their specific contribution in attention deficit. METHOD: We selected 24 patients with CM II and 24 without CM II. DSM-IV criteria and a neuropsychological analysis were applied in all. All patients underwent full night polysomnography. RESULTS: 14 CM II patients presented sleep apnea syndrome, REM sleep behavior disorder and periodic limb movement in sleep; six patients without CM II presented sleep apnea syndrome. Among these patients, 12 (six with CM II and six without CM II) presented attention deficit related to the sleep disorders. CONCLUSION: Sleep disorders may impair cognitive functions, as attention, and contribute to poor quality of learning also in patients with CM II.

Sleep disorder: a possible cause of attention deficit in children and adolescents with Chiari malformation type II / Distúrbios do sono: possível causa de déficit de atenção em crianças e adolescentes com malformação de Chiari tipo II

BACKGROUND: Attention deficit may be related to sleep disorders in Chiari malformation type II (CMII). Our aim is identify sleep disorders and their specific contribution in attention deficit. METHOD: We selected 24 patients with CM II and 24 without CM II. DSM-IV criteria and a neuropsychological analysis were applied in all. All patients underwent full night polysomnography. RESULTS: 14 CM II patients presented sleep apnea syndrome, REM sleep behavior disorder and periodic limb movement in sleep; six patients without CM II presented sleep apnea syndrome. Among these patients, 12 (six with CM II and six without CM II) presented attention deficit related to the sleep disorders. CONCLUSION: Sleep disorders may impair cognitive functions, as attention, and contribute to poor quality of learning also in patients with CM II.

INTRODUÇÃO: Déficits de atenção podem estar relacionados a distúrbios do sono em indivíduos com malformação de Chiari tipo II (CM II). Nosso objetivo é identificar distúrbios do sono e sua contribuição para a ocorrência de déficit de atenção. MÉTODO: Foram selecionados 24 pacientes com CM II e 24 sem CM II. Todos foram submetidos à avaliação neuropsicológica, aos critérios do DSM-IV e a polissonografia. RESULTADOS: 14 pacientes com CM II apresentaram síndrome da apnéia do sono, distúrbio do comportamento da fase do sono REM e movimentos periódicos dos membros em sono; seis pacientes sem CM II apresentaram síndrome da apnéia do sono. Entre estes pacientes, 12 (seis com CM II e seis sem CM II) apresentaram déficit de atenção relacionado a distúrbios do sono. CONCLUSÃO: Distúrbios do sono podem prejudicar funções cognitivas, como a atenção, contribuindo para a piora da qualidade de aprendizado também em pacientes com CM II.

[Violent behavior during sleep]. / Violência durante o sono.

Cases of violent behavior during sleep have been reported in the literature. However, the incidence of violent behavior during sleep is not known. One epidemiological study showed that approximately 2% of the general population, predominantly males, presented violent behavior while asleep. In the present study, the authors describe clinical and medico-legal aspects involved in violent behavior investigation. Violent behavior refers to self-injury or injury to another during sleep. It happens most frequently following partial awakening in the context of arousal disorders (parasomnias). The most frequently diagnosed sleep disorders are REM behavior disorder and somnambulism. Violent behavior might be precipitated by stress, use of alcohol or drugs, sleep deprivation or fever.

Violência durante o sono / Violent behavior during sleep

Casos de comportamento violento (CV) durante o sono são relatados na literatura. A incidência de comportamento violento durante o sono não é muito conhecida. Um estudo epidemiológico mostra que cerca de 2 por cento da população geral apresentava comportamento violento dormindo e eram predominantemente homens. Neste artigo, os autores descrevem aspectos clínicos e médico-legais envolvidos na investigação do comportamento violento. O comportamento violento se refere a ferimentos auto-infligidos ou infligidos a um terceiro durante o sono. Ocorre, muito freqüentemente, seguindo um despertar parcial no contexto de um transtorno de despertar (parassonias). Os transtornos do sono predominantes diagnosticados são: transtorno de comportamento REM e sonambulismo. O comportamento violento poderia ser precipitado pelo estresse, uso de álcool e drogas, privação do sono ou febre.